AB1474 EFFECTIVENESS AND SAFETY OF CURRENT TREATMENT STRATEGIES FOR VEXAS SYNDROME: A SYSTEMATIC REVIEW
Authors: Z. Boyadzhieva, N. Ruffer, I. Kötter, M. Krusche
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> VEXAS syndrome is an adult-onset systemic autoinflammatory condition caused by an acquired deficiency of the <i>UBA1</i> gene in hematopoietic progenitor cells. Its clinical course includes relapsing and refractory inflammatory conditions with high mortality. Optimal treatment strategies remain elusive and need further investigations. <h3>Objectives</h3> To investigate the effectiveness and safety of treatments for VEXAS syndrome. <h3>Methods</h3> A systematic review of the literature in line with the PRISMA guidelines was conducted: MEDLINE, Embase and Cochrane Central Register of Controlled Trials were searched for reports on treatment strategies for VEXAS. Treatment response was recorded as complete (CR), partial (PR) or none (NR) depending on changes in clinical symptoms and laboratory parameters. Patient characteristics, safety data and previous treatments were analyzed. <h3>Results</h3> We identified 32 publications with a total of 83 patients. 97.6% of patients were male. Mean age at disease onset was 68 years (reported for 80/83). Mean follow up was 15.7 months (reported for 23/83). The most frequently used was azacitidine (AZA) (39.8%, 33/83): CR was reported for 9 patients (27.3%, 9/33) and PR for 11 (33.3%, 11/33) (Fig. 1). Further reports included tocilizumab (13.3%, 11/83), allogeneic stem cell transplantation (ASCT) (8.4%, 7/83), glucocorticoid (GC) monotherapy (7.2%, 6/83), anakinra (3.6%, 3/83). Details on response are shown in <b>Table 1</b>. Data on adverse events was available for 29 patients (34.5%). Most common were infections (24.1%, 7/29), herpes zoster reactivation (6.7%, 2/29), cytopenias (13.8%, 4/29). The median number of previous treatments was 3 [IQR 2-5]. A total of 307 prior treatments were reported. In most cases (37.4%, 115/307), details on response and reasons for discontinuation were not reported. Nonresponse to therapy (30.2%, 58/192), GC dependence (22.4%, 43/192) and adverse events (11.9%, 23/192) were common triggers for therapy adjustment. Janus kinase inhibition has been reported to be beneficial in one case series (Heiblig et al., 2022). Individual patient data from this study was not available and, thus, not included in this analysis. <h3>Conclusion</h3> The current data on VEXAS treatment mainly stems from case reports/series and is inhomogeneous. Reporting of treatment response varies, complicating conclusions on treatment efficacy. Most patients received multiple therapies with mixed results. AZA appears promising for a subset of patients. IL-6 inhibition seems beneficial, but a risk of infections should be considered. Ciclosporine was commonly used as an add-on to IL-1 inhibitors suggesting benefits of combination therapy. In general, adverse events are scarcely reported, which hinders an objective risk-benefit assessment. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Zhivana Boyadzhieva: None declared, Nikolas Ruffer: None declared, Ina Kötter Speakers bureau: Novartis, Sobi, Martin Krusche Speakers bureau: Sobi, Novartis, Roche, Grant/research support from: Sobi, Novartis.